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. 2012 May;26(5):1140-3.
doi: 10.1038/leu.2011.325. Epub 2011 Nov 18.

Blockade of JAK2-mediated extrinsic survival signals restores sensitivity of CML cells to ABL inhibitors

E Traer, R MacKenzie, J Snead, A Agarwal, A M Eiring, T O'Hare, B J Druker, M W Deininger

Blockade of JAK2-mediated extrinsic survival signals restores sensitivity of CML cells to ABL inhibitors

E Traer et al. Leukemia. 2012 May.
No abstract available

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Figures

Figure 1
Figure 1. Protection by HS-5 CM is abrogated by JAK2 inhibition
(A) K562 cells were treated with the indicated combinations of imatinib and TG101209, or (B) CYT387, for 60 hours in RM or CM and apoptosis was assessed by Annexin-V staining. (C) CML CD34+ cells were cultured in 24-well plates in media alone or in direct contact with irradiated HS-5 cells for four days, then removed and re-plated in Methocult for 15 days, and CFU-GM colonies counted. Results are normalized to the number of colonies from each untreated condition and combined results from six CML patient samples are shown (N=6). Error bars represent standard error of the mean. Statistically significant differences are represented by *, which signifies p<0.05 by paired t-test.
Figure 2
Figure 2. Combination of ABL and JAK2 inhibitors in an in vivo mouse model of CML reduces BCR-ABL+ cells but also normal hematopoietic cells
(A) Kaplan-Meier curves show survival of mice treated with the indicated inhibitors. The table indicates inhibitor dosage and the number of mice per treatment group. One mouse in the high-dose combination cohort died from gavage and was removed from the survival analysis, *. (B, C) Box-and-whisker plots demonstrate spleen and liver weights at the time of autopsy. Mice treated with the high-dose combination were sacrificed for autopsy and analysis on day 27 due to concerns of toxicity. Mice treated with nilotinib monotherapy and low-dose combination were sacrificed for autopsy and analysis on day 42 (D) Representative histopathology of spleen, liver, and bone marrow at the time of autopsy. Hematoxylin and eosin (H&E) staining was performed on formalin fixed tissues. (E, F) Box-and-whisker plots show the percentage of GFP-positive cells by FACS in the spleen and bone marrow at the time of autopsy.
See this image and copyright information in PMC

References

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